The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform

Brian H Harvey - One of the best experts on this subject based on the ideXlab platform.

  • BRIEF COMMUNICATION The Styrene Metabolite, Phenylglyoxylic Acid, Induces Striatal- Motor Toxicity in the Rat: Influence of Dose Escalation/Reduction over Time
    2013
    Co-Authors: Nicolette Heyer, Lodewyk J Mienie, Cornelius J Van Der Schyf, Heyer N. J. J. Bergh, Brian H Harvey
    Abstract:

    Ó The Author(s) 2010. This article is published with open access at Springerlink.com Abstract Exposure to the industrial solvent, styrene, induces locomotor and cognitive dysfunction in rats, and parkinsonian-like manifestations in man. The antipsychotic, haloperidol (HP), well known to induce striatal toxicity in man and animals, and styrene share a common metabolic pathway yielding p-fluoro Phenylglyoxylic Acid and Phenylglyoxylic Acid (PGA), respectively. Using an exposure period of 30 days and the vacous chewing movement (VCM) model as an expression of striatal-motor toxicity, we found that incremental PGA dosing (220–400 mg/kg) significantly increased VCMs up to day 25, but decreased to control levels shortly after reaching maximum dose. However, a diminishing dose of PGA (400–200 mg/kg) did not evoke an immediate worsening of VCMs but precipitated a significant increase in VCMs following dosage reduction to 200 mg/kg on day 22. PGA exposure, therefore, compromises striatal-motor function that is especially sensitive to changes in exposure dose. Longer alternating dose exposure studies are needed t

  • the styrene metabolite Phenylglyoxylic Acid induces striatal motor toxicity in the rat influence of dose escalation reduction over time
    Neurotoxicity Research, 2011
    Co-Authors: Gisella Terreblanche, Nicolette Heyer, Jacobus J Bergh, Lodewyk J Mienie, Cornelius J Van Der Schyf, Brian H Harvey
    Abstract:

    Exposure to the industrial solvent, styrene, induces locomotor and cognitive dysfunction in rats, and parkinsonian-like manifestations in man. The antipsychotic, haloperidol (HP), well known to induce striatal toxicity in man and animals, and styrene share a common metabolic pathway yielding p-fluoro Phenylglyoxylic Acid and Phenylglyoxylic Acid (PGA), respectively. Using an exposure period of 30 days and the vacous chewing movement (VCM) model as an expression of striatal-motor toxicity, we found that incremental PGA dosing (220–400 mg/kg) significantly increased VCMs up to day 25, but decreased to control levels shortly after reaching maximum dose. However, a diminishing dose of PGA (400–200 mg/kg) did not evoke an immediate worsening of VCMs but precipitated a significant increase in VCMs following dosage reduction to 200 mg/kg on day 22. PGA exposure, therefore, compromises striatal-motor function that is especially sensitive to changes in exposure dose. Longer alternating dose exposure studies are needed to establish whether motor dysfunction is progressive in severity or longevity. These findings are of significance for the environmental toxicology of styrene in the chemical industry.

Yun-chao Kan - One of the best experts on this subject based on the ideXlab platform.

  • directed evolution of formate dehydrogenase and its application in the biosynthesis of l phenylglycine from Phenylglyoxylic Acid
    Molecular Catalysis, 2021
    Co-Authors: Cun-duo Tang, Hong-ling Shi, Yun-chao Kan, Zhenhua Zhang, Yuli Xie, Tiantian Yang, Sipu Zhang, Fanghui Bai, Lun-guang Yao
    Abstract:

    Abstract Formate dehydrogenase (FDH) is a d -2‑hydroxy Acid dehydrogenase, and catalyzes the oxidation of formate to carbon dioxide, coupled with reduction of NAD+ to NADH that plays a key role in the process of NADH regeneration. In order to obtain high activity formate dehydrogenase mutants, the formate dehydrogenase CbFDHC23S was used as the parent to conduct two rounds of directed evolution, and a mutant M2 was obtained which specific activity was about 4 times more than the parent and was more suitable for coenzyme regeneration under physiological conditions. Then, the molecular mechanism of temperature characteristic and catalytic efficiency change was preliminarily elucidated by computer-aided method. Finally, an engineered E. coli strain was established to co-express formate dehydrogenase and l -leucine dehydrogenase and enantioselectively transform Phenylglyoxylic Acid to give l - phenylglycine (e.e. >99%), the yield and space-time yield of l - phenylglycine can reach 90.46% and 82.07 g·L−1·d−1. This study laid a theoretical foundation for the green biosynthesis of food additives such as chiral alcohols and amino Acid derivatives catalyzed by FDH coupling to enhance the regeneration capacity of NADH, reduce the regeneration cost of NADH, and achieve high efficiency and low cost.

  • one pot synthesis of Phenylglyoxylic Acid from racemic mandelic Acids via cascade biocatalysis
    Journal of Agricultural and Food Chemistry, 2019
    Co-Authors: Cun-duo Tang, Peng-ju Ding, Hong-ling Shi, Yuan-yuan Jia, Mao-zhi Zhou, Lun-guang Yao, Yun-chao Kan
    Abstract:

    Phenylglyoxylic Acid (PGA) are key building blocks and widely used to synthesize pharmaceutical intermediates or food additives. However, the existing synthetic methods for PGA generally involve toxic cyanide and complex processes. To explore an alternative method for PGA biosynthesis, we envisaged cascade biocatalysis for the one-pot synthesis of PGA from racemic mandelic Acid. A novel mandelate racemase named ArMR showing higher expression level (216.9 U·mL-1 fermentation liquor) was cloned from Agrobacterium radiobacter and identified, and six recombinant Escherichia coli strains were engineered to coexpress three enzymes of mandelate racemase, d-mandelate dehydrogenase and l-lactate dehydrogenase, and transform racemic mandelic Acid to PGA. Among them, the recombinant E. coli TCD 04, engineered to coexpress three enzymes of ArMR, LhDMDH, and LhLDH, can transform racemic mandelic Acid (100 mM) to PGA with 98% conversion. Taken together, we provide a green approach for one-pot biosynthesis of PGA from racemic mandelic Acid.

  • One-Pot Synthesis of Phenylglyoxylic Acid from Racemic Mandelic Acids via Cascade Biocatalysis
    2019
    Co-Authors: Cun-duo Tang, Peng-ju Ding, Hong-ling Shi, Yuan-yuan Jia, Mao-zhi Zhou, Lun-guang Yao, Yun-chao Kan
    Abstract:

    Phenylglyoxylic Acid (PGA) are key building blocks and widely used to synthesize pharmaceutical intermediates or food additives. However, the existing synthetic methods for PGA generally involve toxic cyanide and complex processes. To explore an alternative method for PGA biosynthesis, we envisaged cascade biocatalysis for the one-pot synthesis of PGA from racemic mandelic Acid. A novel mandelate racemase named ArMR showing higher expression level (216.9 U·mL–1 fermentation liquor) was cloned from Agrobacterium radiobacter and identified, and six recombinant Escherichia coli strains were engineered to coexpress three enzymes of mandelate racemase, d-mandelate dehydrogenase and l-lactate dehydrogenase, and transform racemic mandelic Acid to PGA. Among them, the recombinant E. coli TCD 04, engineered to coexpress three enzymes of ArMR, LhDMDH, and LhLDH, can transform racemic mandelic Acid (100 mM) to PGA with 98% conversion. Taken together, we provide a green approach for one-pot biosynthesis of PGA from racemic mandelic Acid

  • biosynthesis of Phenylglyoxylic Acid by lhdmdh a novel d mandelate dehydrogenase with high catalytic activity
    Journal of Agricultural and Food Chemistry, 2018
    Co-Authors: Cun-duo Tang, Peng-ju Ding, Hong-ling Shi, Lun-guang Yao, Zhujin Jiao, Fei Liu, Hongfei Shi, Yun-chao Kan
    Abstract:

    d-Mandelate dehydrogenase (DMDH) has the potential to convert d-mandelic Acid to Phenylglyoxylic Acid (PGA), which is a key building block in the field of chemical synthesis and is widely used to synthesize pharmaceutical intermediates or food additives. A novel NAD+-dependent d-mandelate dehydrogenase was cloned from Lactobacillus harbinensi (LhDMDH) by genome mining and expressed in Escherichia coli BL21. After being purified to homogeneity, the oxidation activity of LhDMDH toward d-mandelic Acid was approximately 1200 U·mg–1, which was close to four times the activity of the probe. Meanwhile, the kcat/Km value of LhDMDH was 28.80 S–1·mM–1, which was distinctly higher than the probe. By coculturing two E. coli strains expressing LhDMDH and LcLDH, we developed a system for the efficient synthesis of PGA, achieving a 60% theoretical yield and 99% purity without adding coenzyme or cosubstrate. Our data supports the implementation of a promising strategy for the chiral resolution of racemic mandelic Acid an...

  • Biosynthesis of Phenylglyoxylic Acid by LhDMDH, a Novel d‑Mandelate Dehydrogenase with High Catalytic Activity
    2018
    Co-Authors: Cun-duo Tang, Peng-ju Ding, Hong-ling Shi, Lun-guang Yao, Zhujin Jiao, Fei Liu, Hongfei Shi, Yun-chao Kan
    Abstract:

    d-Mandelate dehydrogenase (DMDH) has the potential to convert d-mandelic Acid to Phenylglyoxylic Acid (PGA), which is a key building block in the field of chemical synthesis and is widely used to synthesize pharmaceutical intermediates or food additives. A novel NAD+-dependent d-mandelate dehydrogenase was cloned from Lactobacillus harbinensi (LhDMDH) by genome mining and expressed in Escherichia coli BL21. After being purified to homogeneity, the oxidation activity of LhDMDH toward d-mandelic Acid was approximately 1200 U·mg–1, which was close to four times the activity of the probe. Meanwhile, the kcat/Km value of LhDMDH was 28.80 S–1·mM–1, which was distinctly higher than the probe. By coculturing two E. coli strains expressing LhDMDH and LcLDH, we developed a system for the efficient synthesis of PGA, achieving a 60% theoretical yield and 99% purity without adding coenzyme or cosubstrate. Our data supports the implementation of a promising strategy for the chiral resolution of racemic mandelic Acid and the biosynthesis of PGA

Mei-tian Xiao - One of the best experts on this subject based on the ideXlab platform.

  • Kinetics of Asymmetric Reduction of Phenylglyoxylic Acid to R-(-)-Mandelic Acid by Saccharomyces Cerevisiae FD11b
    Chinese Journal of Chemical Engineering, 2006
    Co-Authors: Mei-tian Xiao, Yayan Huang, Chun Meng, Yanghao Guo
    Abstract:

    Abstract The kinetics of asymmetric production of R-(–)-mandelic Acid (R-MA) from Phenylglyoxylic Acid (PGA) catalyzed by Saccharomyces cerevisiae sp. strain FD11b was studied by fed-batch cultures. The concentrations of glucose and PGA were controlled respectively with a dual feeding system. When the electron donor glucose was supplied at the rate of 0.0833mmol·gdw−1·h−1, the specific production rate (qp) and the enantiomeric excess of R-MA reached the maximum 0.353mmol·gdw−1·h−1 and 97.1%, respectively. The apparent reduction activity of yeast FD11b was obviously affected by both substrate PGA and product MA. The qp value reached the maximum 0.36—0.38mmol-gdw−1·h−1 when the PGA concentration was controlled between 25 and 35mmol·L−1. The obvious substrate inhibition of bioconversion was observed at the PGA concentrations higher than 40mmol·L−1. The accumulation of product MA also caused a severe feed-back inhibition for its production when the product concentration was above 60mmol·L−1. The kinetic model with the inhibition effect of both substrate and product was simulated by a computer-based least-square arithmatic. The established kinetic model was in good agreement with the experimental data.

  • bioreduction of Phenylglyoxylic Acid to r mandelic Acid by saccharomyces cerevisiae fd11b
    Enzyme and Microbial Technology, 2005
    Co-Authors: Mei-tian Xiao, Yayan Huang, Xianai Shi, Yanghao Guo
    Abstract:

    Abstract Screening from 40 microorganisms belonging to different taxonomical groups ( Saccharomyces cerevisiae , Lactoballius, Streptococcus faecalis and Candida albicans ) was performed to select the strain with high production rate of R-(−)-mandelic Acid (R-MA). A sp. strain S. cerevisiae FD11b with high yield and enantiomeric excess (e.e.) and little byproducts was obtained by means of UV-mutation breeding. In the optimal conditions of pH 6.5, 32 °C, anaerobic and glucose supply rate ( F glu ) 0.0833 mmol gdw −1  h −1 , the strain FD11b showed a high specific MA production rate ( q p  = 0.35 mmol gdw −1  h −1 ) and enantioselectivity (e.e. = 97.1%). The Phenylglyoxylic Acid (PGA) concentration showed a remarkable effect on the apparent activity of MA dehydrogenase. The specific production rate ( q p ) reached the maximum at 30–40 mM of PGA concentrations. At higher concentrations of PGA more than 40 mM, the q p decreased obviously in a linear way. However, the e.e. of R-MA kept about 95–96.5%, when the PGA concentration was below 60 mM, even at the concentration of PGA 80 mM, the e.e. was still higher than 90%. A modified Monod type equation based on a hypothesis of substrate inhibition could fit the experimental data well. The estimated maximum specific production rate ( q pm ) and saturation constant ( K s ) were 0.431 mmol gdw −1  h −1 and 5.88 mM, respectively.

Cun-duo Tang - One of the best experts on this subject based on the ideXlab platform.

  • directed evolution of formate dehydrogenase and its application in the biosynthesis of l phenylglycine from Phenylglyoxylic Acid
    Molecular Catalysis, 2021
    Co-Authors: Cun-duo Tang, Hong-ling Shi, Yun-chao Kan, Zhenhua Zhang, Yuli Xie, Tiantian Yang, Sipu Zhang, Fanghui Bai, Lun-guang Yao
    Abstract:

    Abstract Formate dehydrogenase (FDH) is a d -2‑hydroxy Acid dehydrogenase, and catalyzes the oxidation of formate to carbon dioxide, coupled with reduction of NAD+ to NADH that plays a key role in the process of NADH regeneration. In order to obtain high activity formate dehydrogenase mutants, the formate dehydrogenase CbFDHC23S was used as the parent to conduct two rounds of directed evolution, and a mutant M2 was obtained which specific activity was about 4 times more than the parent and was more suitable for coenzyme regeneration under physiological conditions. Then, the molecular mechanism of temperature characteristic and catalytic efficiency change was preliminarily elucidated by computer-aided method. Finally, an engineered E. coli strain was established to co-express formate dehydrogenase and l -leucine dehydrogenase and enantioselectively transform Phenylglyoxylic Acid to give l - phenylglycine (e.e. >99%), the yield and space-time yield of l - phenylglycine can reach 90.46% and 82.07 g·L−1·d−1. This study laid a theoretical foundation for the green biosynthesis of food additives such as chiral alcohols and amino Acid derivatives catalyzed by FDH coupling to enhance the regeneration capacity of NADH, reduce the regeneration cost of NADH, and achieve high efficiency and low cost.

  • one pot synthesis of Phenylglyoxylic Acid from racemic mandelic Acids via cascade biocatalysis
    Journal of Agricultural and Food Chemistry, 2019
    Co-Authors: Cun-duo Tang, Peng-ju Ding, Hong-ling Shi, Yuan-yuan Jia, Mao-zhi Zhou, Lun-guang Yao, Yun-chao Kan
    Abstract:

    Phenylglyoxylic Acid (PGA) are key building blocks and widely used to synthesize pharmaceutical intermediates or food additives. However, the existing synthetic methods for PGA generally involve toxic cyanide and complex processes. To explore an alternative method for PGA biosynthesis, we envisaged cascade biocatalysis for the one-pot synthesis of PGA from racemic mandelic Acid. A novel mandelate racemase named ArMR showing higher expression level (216.9 U·mL-1 fermentation liquor) was cloned from Agrobacterium radiobacter and identified, and six recombinant Escherichia coli strains were engineered to coexpress three enzymes of mandelate racemase, d-mandelate dehydrogenase and l-lactate dehydrogenase, and transform racemic mandelic Acid to PGA. Among them, the recombinant E. coli TCD 04, engineered to coexpress three enzymes of ArMR, LhDMDH, and LhLDH, can transform racemic mandelic Acid (100 mM) to PGA with 98% conversion. Taken together, we provide a green approach for one-pot biosynthesis of PGA from racemic mandelic Acid.

  • One-Pot Synthesis of Phenylglyoxylic Acid from Racemic Mandelic Acids via Cascade Biocatalysis
    2019
    Co-Authors: Cun-duo Tang, Peng-ju Ding, Hong-ling Shi, Yuan-yuan Jia, Mao-zhi Zhou, Lun-guang Yao, Yun-chao Kan
    Abstract:

    Phenylglyoxylic Acid (PGA) are key building blocks and widely used to synthesize pharmaceutical intermediates or food additives. However, the existing synthetic methods for PGA generally involve toxic cyanide and complex processes. To explore an alternative method for PGA biosynthesis, we envisaged cascade biocatalysis for the one-pot synthesis of PGA from racemic mandelic Acid. A novel mandelate racemase named ArMR showing higher expression level (216.9 U·mL–1 fermentation liquor) was cloned from Agrobacterium radiobacter and identified, and six recombinant Escherichia coli strains were engineered to coexpress three enzymes of mandelate racemase, d-mandelate dehydrogenase and l-lactate dehydrogenase, and transform racemic mandelic Acid to PGA. Among them, the recombinant E. coli TCD 04, engineered to coexpress three enzymes of ArMR, LhDMDH, and LhLDH, can transform racemic mandelic Acid (100 mM) to PGA with 98% conversion. Taken together, we provide a green approach for one-pot biosynthesis of PGA from racemic mandelic Acid

  • biosynthesis of Phenylglyoxylic Acid by lhdmdh a novel d mandelate dehydrogenase with high catalytic activity
    Journal of Agricultural and Food Chemistry, 2018
    Co-Authors: Cun-duo Tang, Peng-ju Ding, Hong-ling Shi, Lun-guang Yao, Zhujin Jiao, Fei Liu, Hongfei Shi, Yun-chao Kan
    Abstract:

    d-Mandelate dehydrogenase (DMDH) has the potential to convert d-mandelic Acid to Phenylglyoxylic Acid (PGA), which is a key building block in the field of chemical synthesis and is widely used to synthesize pharmaceutical intermediates or food additives. A novel NAD+-dependent d-mandelate dehydrogenase was cloned from Lactobacillus harbinensi (LhDMDH) by genome mining and expressed in Escherichia coli BL21. After being purified to homogeneity, the oxidation activity of LhDMDH toward d-mandelic Acid was approximately 1200 U·mg–1, which was close to four times the activity of the probe. Meanwhile, the kcat/Km value of LhDMDH was 28.80 S–1·mM–1, which was distinctly higher than the probe. By coculturing two E. coli strains expressing LhDMDH and LcLDH, we developed a system for the efficient synthesis of PGA, achieving a 60% theoretical yield and 99% purity without adding coenzyme or cosubstrate. Our data supports the implementation of a promising strategy for the chiral resolution of racemic mandelic Acid an...

  • Biosynthesis of Phenylglyoxylic Acid by LhDMDH, a Novel d‑Mandelate Dehydrogenase with High Catalytic Activity
    2018
    Co-Authors: Cun-duo Tang, Peng-ju Ding, Hong-ling Shi, Lun-guang Yao, Zhujin Jiao, Fei Liu, Hongfei Shi, Yun-chao Kan
    Abstract:

    d-Mandelate dehydrogenase (DMDH) has the potential to convert d-mandelic Acid to Phenylglyoxylic Acid (PGA), which is a key building block in the field of chemical synthesis and is widely used to synthesize pharmaceutical intermediates or food additives. A novel NAD+-dependent d-mandelate dehydrogenase was cloned from Lactobacillus harbinensi (LhDMDH) by genome mining and expressed in Escherichia coli BL21. After being purified to homogeneity, the oxidation activity of LhDMDH toward d-mandelic Acid was approximately 1200 U·mg–1, which was close to four times the activity of the probe. Meanwhile, the kcat/Km value of LhDMDH was 28.80 S–1·mM–1, which was distinctly higher than the probe. By coculturing two E. coli strains expressing LhDMDH and LcLDH, we developed a system for the efficient synthesis of PGA, achieving a 60% theoretical yield and 99% purity without adding coenzyme or cosubstrate. Our data supports the implementation of a promising strategy for the chiral resolution of racemic mandelic Acid and the biosynthesis of PGA

Yanghao Guo - One of the best experts on this subject based on the ideXlab platform.

  • Kinetics of Asymmetric Reduction of Phenylglyoxylic Acid to R-(-)-Mandelic Acid by Saccharomyces Cerevisiae FD11b
    Chinese Journal of Chemical Engineering, 2006
    Co-Authors: Mei-tian Xiao, Yayan Huang, Chun Meng, Yanghao Guo
    Abstract:

    Abstract The kinetics of asymmetric production of R-(–)-mandelic Acid (R-MA) from Phenylglyoxylic Acid (PGA) catalyzed by Saccharomyces cerevisiae sp. strain FD11b was studied by fed-batch cultures. The concentrations of glucose and PGA were controlled respectively with a dual feeding system. When the electron donor glucose was supplied at the rate of 0.0833mmol·gdw−1·h−1, the specific production rate (qp) and the enantiomeric excess of R-MA reached the maximum 0.353mmol·gdw−1·h−1 and 97.1%, respectively. The apparent reduction activity of yeast FD11b was obviously affected by both substrate PGA and product MA. The qp value reached the maximum 0.36—0.38mmol-gdw−1·h−1 when the PGA concentration was controlled between 25 and 35mmol·L−1. The obvious substrate inhibition of bioconversion was observed at the PGA concentrations higher than 40mmol·L−1. The accumulation of product MA also caused a severe feed-back inhibition for its production when the product concentration was above 60mmol·L−1. The kinetic model with the inhibition effect of both substrate and product was simulated by a computer-based least-square arithmatic. The established kinetic model was in good agreement with the experimental data.

  • bioreduction of Phenylglyoxylic Acid to r mandelic Acid by saccharomyces cerevisiae fd11b
    Enzyme and Microbial Technology, 2005
    Co-Authors: Mei-tian Xiao, Yayan Huang, Xianai Shi, Yanghao Guo
    Abstract:

    Abstract Screening from 40 microorganisms belonging to different taxonomical groups ( Saccharomyces cerevisiae , Lactoballius, Streptococcus faecalis and Candida albicans ) was performed to select the strain with high production rate of R-(−)-mandelic Acid (R-MA). A sp. strain S. cerevisiae FD11b with high yield and enantiomeric excess (e.e.) and little byproducts was obtained by means of UV-mutation breeding. In the optimal conditions of pH 6.5, 32 °C, anaerobic and glucose supply rate ( F glu ) 0.0833 mmol gdw −1  h −1 , the strain FD11b showed a high specific MA production rate ( q p  = 0.35 mmol gdw −1  h −1 ) and enantioselectivity (e.e. = 97.1%). The Phenylglyoxylic Acid (PGA) concentration showed a remarkable effect on the apparent activity of MA dehydrogenase. The specific production rate ( q p ) reached the maximum at 30–40 mM of PGA concentrations. At higher concentrations of PGA more than 40 mM, the q p decreased obviously in a linear way. However, the e.e. of R-MA kept about 95–96.5%, when the PGA concentration was below 60 mM, even at the concentration of PGA 80 mM, the e.e. was still higher than 90%. A modified Monod type equation based on a hypothesis of substrate inhibition could fit the experimental data well. The estimated maximum specific production rate ( q pm ) and saturation constant ( K s ) were 0.431 mmol gdw −1  h −1 and 5.88 mM, respectively.